Abstract Each year several hundred thousand Americans suffer short term lung failure requiring respiratory support within the intensive care unit. The objective of this proposal is to develop a percutaneous respiratory assist catheter (PRAC) that can be inserted into the venous system to provide supplemental breathing support, independent of the lungs, for patients requiring short-term (~ 4-7 day) respiratory assistance. The PRAC will be designed for percutaneous insertion into a peripheral vein and placement in the central venous system, where it will be exposed to all the blood returning to the heart. The PRAC will use a rotating impeller within the fiber bundle to generate active mixing of blood to enhance gas exchange. We will also develop novel hollow fiber membranes that incorporate immobilized enzymes that will further accelerate CO2 removal. The specific aims of the project are to: 1. Design and evaluate new mixing impeller structures that increase CO2 removal by increasing fluid motion into and within the hollow fiber bundle. The designs will be developed using computational fluid dynamics (CFD). 2. Develop an enzymatic coating of carbonic anhydrase to accelerate CO2 removal and improve the biocompatibility of hollow fiber membranes. 3. Perform acute (6 hour) and chronic (7 day) calf implants of the PRAC to assess gas exchange, cardiovascular impact, and biocompatibility. Our target is a percutaneous assist catheter (20-25 Fr or smaller) that can provide 90-120 ml/min of CO2 removal when used as an adjuvant or replacement to existing therapy for patients with acute lung failure (ARDS, pneumonia) or acute on chronic lung failure (COPD with exacerbation). Project Narrative Several hundred thousand Americans each year suffer from short-term lung failure that requires hospitalization so that breathing support for the patient can be provided. The current methods for providing breathing support to these patients have problems and complications associated with them. The proposed project will develop a simple catheter that can be inserted into a patient's vein to provide breathing support while allowing the lungs to rest and heal.